Development of BromoTag: a “bump-and-hole”–PROTAC system to induce potent, rapid, and selective degradation of tagged target proteins

AG Bond, C Craigon, KH Chan, A Testa… - Journal of Medicinal …, 2021 - ACS Publications
Small-molecule-induced protein depletion technologies, also called inducible degrons,
allow degradation of genetically engineered target proteins within cells and animals. Here …

Rapid and reversible knockdown of endogenously tagged endosomal proteins via an optimized HaloPROTAC degrader

H Tovell, A Testa, C Maniaci, H Zhou… - ACS Chemical …, 2019 - ACS Publications
Inducing post-translational protein knockdown is an important approach to probe biology
and validate drug targets. An efficient strategy to achieve this involves expression of a …

The dTAG system for immediate and target-specific protein degradation

B Nabet, JM Roberts, DL Buckley, J Paulk… - Nature chemical …, 2018 - nature.com
Dissection of complex biological systems requires target-specific control of the function or
abundance of proteins. Genetic perturbations are limited by off-target effects …

Structure-guided design of a “bump-and-hole” bromodomain-based degradation tag

RP Nowak, Y Xiong, N Kirmani… - Journal of Medicinal …, 2021 - ACS Publications
Chemical biology tools to modulate protein levels in cells are critical to decipher complex
biology. Targeted protein degradation offers the potential for rapid and dose-dependent …

[HTML][HTML] Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules

B Nabet, FM Ferguson, BKA Seong, M Kuljanin… - Nature …, 2020 - nature.com
Chemical biology strategies for directly perturbing protein homeostasis including the
degradation tag (dTAG) system provide temporal advantages over genetic approaches and …

Targeted protein degradation phenotypic studies using HaloTag CRISPR/Cas9 endogenous tagging coupled with HaloPROTAC3

EA Caine, SD Mahan, RL Johnson… - Current Protocols in …, 2020 - Wiley Online Library
To assess the role of a protein, protein loss phenotypic studies can be used, most commonly
through mutagenesis RNAi or CRISPR knockout. Such studies have been critical for the …

Continuous evolution of compact protein degradation tags regulated by selective molecular glues

JAM Mercer, SJ DeCarlo, SS Roy Burman, V Sreekanth… - Science, 2024 - science.org
Conditional protein degradation tags (degrons) are usually> 100 amino acids long or are
triggered by small molecules with substantial off-target effects, thwarting their use as specific …

HiBiT-SpyTag: A Minimal Tag for Covalent Protein Capture and Degrader Development

T Tsang, F Huerta, Y Liu, J Che, RJ Metivier… - ACS Chemical …, 2023 - ACS Publications
The ability to rapidly and selectively modulate cellular protein levels using small molecules
is essential for studying complex biological systems. Degradation tags, such as dTAG, allow …

Ligand-induced genetic degradation as a tool for target validation

A Yesbolatova, Y Tominari, MT Kanemaki - Drug Discovery Today …, 2019 - Elsevier
Targeted protein degraders, known as proteolysis targeting chimeras (PROTACs), are
drawing more attention as next-generation drugs to target currently undruggable proteins …

[PDF][PDF] Inducible degradation of target proteins through a tractable affinity-directed protein missile system

LM Simpson, TJ Macartney, A Nardin, LJ Fulcher… - Cell Chemical …, 2020 - cell.com
The affinity-directed protein missile (AdPROM) system utilizes specific polypeptide binders
of intracellular proteins of interest (POIs) conjugated to an E3 ubiquitin ligase moiety to …